Cache Valley Virus (CVV) has been shown to be an important cause of severe birth defects in sheep in the U.S. The fact that the virus replicates in a number of mammals, including humans, suggests it could be a potential teratogen in other species. Transginec sheep which express an antisense CVV gene will be produced to study the effects of expression of antisense viral genes on disease resistance and prevention of congental defects. A pHG-CVV recombinant retrovirus will be used to transfect sheep zygotes. PCR will be performed on transfected embryos to detect gene incorporation. Embryos integrating the gene will be cloned by nuclear transfer to produce multiple transgenic embryos. Embryos will be transferred to recipient ewes and challenged with an in utero inoculation of CVV to determine if viral resistance has occurred, and observed for the absence of congenital defects.